Research Summary

Michelle’s lab develops innovative approaches to screen for chemical tools and drug leads, using biophysical approaches like fragment-based drug discovery and biological approaches including high-content imaging with primary cells and organisms. Our goal is to demonstrate ‘druggability’ of new target classes and to use our compounds to discover new targets for drug discovery. Areas of interest include protein-protein interactions, allosteric and scaffolding sites in enzymes, and orphan and neglected diseases. Michelle is co-Director of the Small Molecule Discovery Center, a collaborative research and core lab that includes a high-throughput screening facility and medicinal chemistry (smdc.ucsf.edu).

Research Funding

Education

1990, Bryn Mawr College, Bryn Mawr, PA, B.A., Chemistry
1997, California Institute of Technology, Pasadena, CA, Ph.D., Chemistry
1999, Genentech, Inc, South San Francisco, CA and Sunesis Pharmaceuticals, Redwood City, CA, Postdoctoral fellowship, Protein Engineering

Honors & Awards

  • 1990    
    European Traveling Fellowship    Bryn Mawr College
  • 1991    
    Blodgett Fellowship    General Electric Foundation
  • 1992    
    Predoctoral Fellowship    National Science Foundation
  • 1995    
    Traineeship    National Institutes of Health
  • 1997    
    Postdoctoral Fellowship    Damon Runyon Cancer Research Foundation 
  • 2014    
    Finalist    SLAS Innovation Award
  • 2018    
    Breakthrough Chemical Biology Awardee    Ono Pharma Foundation     
  • 2018    
    Webster-Sibilsky Keynote Lecture    University of Illinois, Chicago    
  • 2019    
    Briggs Lecture    University of Texas Health San Antonio    
  • 2021    
    Fellow    Society for Laboratory Automation and Screening    
  • 2024    
    Cope Scholar    American Chemical Society, Organic Division    
  • 2024    
    Gordon Hammes Lectureship    American Chemical Society, Biochemisty    

Selected Publications

  1. Maciag AE, Yang Y, Sharma AK, Turner DM, DeHart CJ, Abdelkarim H, Fan L, Smith BP, Kumari V, Dyba M, Rigby M, Castillo Badillo JA, Adams L, Fornelli L, Fox S, Brafman A, Turbyville T, Gillette W, Messing S, Agamasu C, Wolfe AL, Gysin S, Chan AH, Simanshu DK, Esposito D, Chertov O, Stephen AG, Arkin M, Renslo A, Kelleher NL, Gaponenko V, Lightstone FC, Nissley DV, McCormick F. Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine. Proc Natl Acad Sci U S A. 2025 May 13; 122(19):e2410766122.  View on PubMed
  2. Detomasi TC, Degotte G, Huang S, Suryawanshi RK, Diallo A, Lizzadro L, Zaptero-Belinchón FJ, Taha TY, Li J, Richards AL, Hantz ER, Alam Z, Montano M, McCavitt-Malvido M, Gumpena R, Partridge JR, Correy GJ, Matsui Y, Charvat AF, Glenn IS, Rosecrans J, Revalde JL, Anderson D, Hultquist JF, Arkin MR, Neitz RJ, Swaney DL, Krogan NJ, Shoichet BK, Verba KA, Ott M, Renslo AR, Craik CS. Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy. Sci Adv. 2025 Apr 25; 11(17):eadt7836.  View on PubMed
  3. Peck A, Dadi A, Yavarow Z, Alfano LN, Anderson D, Arkin MR, Chou TF, D'Ambrosio ES, Diaz-Manera J, Dudley JP, Elder AG, Ghoshal N, Hart CE, Hart MM, Huryn DM, Johnson AE, Jones KB, Kimonis V, Kiskinis E, Lee EB, Lloyd TE, Mapstone M, Martin A, Meyer H, Mozaffar T, Onyike CU, Pfeffer G, Pindon A, Raman M, Richard I, Rubinsztein DC, Schiava M, Schütz AK, Shen PS, Southworth DR, Staffaroni AM, Taralio-Gravovac M, Weihl CC, Yao Q, Ye Y, Peck N 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.  View on PubMed
  4. Chou J, Robinson TM, Egusa EA, Lodha R, Zhang M, Badura M, Mikayelyan M, Delavan HM, Swinderman J, Wilson C, Zhu J, Das R, Nguyen M, Loehr A, Golsorkhi T, Simmons A, Abida W, Chinnaiyan AM, Arkin MR, Small EJ, Quigley DA, Yang L, Kim M, Ashworth A, Feng FY. Synthetic Lethal Targeting of CDK12-Deficient Prostate Cancer with PARP Inhibitors. Clin Cancer Res. 2024 Dec 02; 30(23):5445-5458.  View on PubMed
  5. Liara Rizzi, Julio C. Rojas, Andrew J. Ambrose, Marcio Luiz Figueredo Balthazar, Michelle R. Arkin, Lea T. Grinberg. D13 caspase-6-cleaved tau, a new biomarker to complement Alzheimer’s disease diagnosis. Alzheimer's & Dementia. 2024 Dec 1; 20(Suppl 8):e095421.  View on PubMed
  6. Ian Michael Oh, Song Hua Li, Felipe Luiz Pereira, Prabhleen Kaur, Anya Raju, Rushil Jerfy, Claudia Kimie Suemoto, Renata Elaine Paraizo Leite, Vitor Ribeiro Paes, Roberta Diehl Rodriguez, Andrew J. Ambrose, Salvatore Spina, William W. Seeley, Bruce L. Miller, Michelle R. Arkin, Lea T. Grinberg. Truncated tau accumulates before hyperphosphorylated tau and in relatively distinct neuronal subpopulations in entorhinal cortex and inferior temporal gyrus in Alzheimer’s disease patients. Alzheimer's & Dementia. 2024 Dec 1; 20(Suppl 1):e093137.  View on PubMed
  7. Gendelev L, Taylor J, Myers-Turnbull D, Chen S, McCarroll MN, Arkin MR, Kokel D, Keiser MJ. Deep phenotypic profiling of neuroactive drugs in larval zebrafish. Nat Commun. 2024 Nov 17; 15(1):9955.  View on PubMed
  8. Theofilas P, Wang C, Butler D, Morales DO, Petersen C, Ambrose A, Chin B, Yang T, Khan S, Ng R, Kayed R, Karch CM, Miller BL, Gestwicki JE, Gan L, Temple S, Arkin MR, Grinberg LT. iPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death. Mol Cell Neurosci. 2024 Sep; 130:103954.  View on PubMed
  9. Somsen BA, Cossar PJ, Arkin MR, Brunsveld L, Ottmann C. 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization. Chembiochem. 2024 Jul 15; 25(14):e202400214.  View on PubMed
  10. Vickery HR, Virta JM, Konstantinidou M, Arkin MR. Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues. SLAS Discov. 2024 Jul; 29(5):100165.  View on PubMed
  11. Silva DB, Trinidad M, Ljungdahl A, Revalde JL, Berguig GY, Wallace W, Patrick CS, Bomba L, Arkin M, Dong S, Estrada K, Hutchinson K, LeBowitz JH, Schlessinger A, Johannesen KM, Møller RS, Giacomini KM, Froelich S, Sanders SJ, Wuster A. Haploinsufficiency underlies the neurodevelopmental consequences of SLC6A1 variants. Am J Hum Genet. 2024 06 06; 111(6):1222-1238.  View on PubMed
  12. Konstantinidou M, Arkin MR. Molecular glues for protein-protein interactions: Progressing toward a new dream. Cell Chem Biol. 2024 Jun 20; 31(6):1064-1088.  View on PubMed
  13. D'Ippolito RA, Rabara D, Blanco MA, Alberico E, Drew MR, Ramakrishnan N, Sontan D, Widmeyer SRT, Scheidemantle GM, Messing S, Turner D, Arkin M, Maciag AE, Stephen AG, Esposito D, McCormick F, Nissley DV, DeHart CJ. A Top-Down Proteomic Assay to Evaluate KRAS4B-Compound Engagement. Anal Chem. 2024 04 02; 96(13):5223-5231.  View on PubMed
  14. Lee JY, Reyes NS, Ravishankar S, Zhou M, Krasilnikov M, Ringler C, Pohan G, Wilson C, Ang KK, Wolters PJ, Tsukui T, Sheppard D, Arkin MR, Peng T. An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis. J Clin Invest. 2024 Mar 07; 134(9).  View on PubMed
  15. Jiang Z, Kuo YH, Arkin MR. Synthetic autophagy receptor. Autophagy. 2024 03; 20(3):701-703.  View on PubMed
  16. Ortiz G, Longbotham JE, Qin SL, Zhang MY, Lee GM, Neitz RJ, Kelly MJS, Arkin MR, Fujimori DG. Identifying ligands for the PHD1 finger of KDM5A through high-throughput screening. RSC Chem Biol. 2024 Mar 06; 5(3):209-215.  View on PubMed
  17. Braxton JR, Altobelli CR, Tucker MR, Tse E, Thwin AC, Arkin MR, Southworth DR. The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions. Nat Struct Mol Biol. 2023 Dec; 30(12):2009-2019.  View on PubMed
  18. Jiang Z, Kuo YH, Arkin MR. Autophagy Receptor-Inspired Antibody-Fusion Proteins for Targeted Intracellular Degradation. J Am Chem Soc. 2023 11 08; 145(44):23939-23947.  View on PubMed
  19. Konstantinidou M, Visser EJ, Vandenboorn E, Chen S, Jaishankar P, Overmans M, Dutta S, Neitz RJ, Renslo AR, Ottmann C, Brunsveld L, Arkin MR. Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments. J Am Chem Soc. 2023 09 20; 145(37):20328-20343.  View on PubMed
  20. Visser EJ, Jaishankar P, Sijbesma E, Pennings MAM, Vandenboorn EMF, Guillory X, Neitz RJ, Morrow J, Dutta S, Renslo AR, Brunsveld L, Arkin MR, Ottmann C. From Tethered to Freestanding Stabilizers of 14-3-3 Protein-Protein Interactions through Fragment Linking. Angew Chem Int Ed Engl. 2023 09 11; 62(37):e202308004.  View on PubMed

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